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Neuromodulation of subchondral bone affects KOA\u2010related pain and involves dorsal root ganglion (DRG). Our previous studies have demonstrated efficacy of icariin (ICA) in treating KOA, but neuromodulation mechanisms in peripheral nerves associated with the treatment of chronic pain in KOA remain unclear. This study aimed to investigate peripheral neuromodulation mechanisms of ICA in KOA\u2010related chronic pain: (1) assessing therapeutic effect of ICA in a rat model of KOA\u2010induced chronic pain; (2) investigating changes in pain\u2010related nerve fibres and transient receptor potential vanilloid Subfamily 1 (TRPV1) pathway in subchondral bone following ICA treatment; and (3) exploring expression of pain\u2010related Nogo\u2010A\/TRPV1 pathway in DRG, thereby elucidating neurotransmission of pain. Experimental results confirmed the curative effect of ICA on KOA by relieving chronic pain and pathological changes. ICA also effectively reduced bone remodelling, the area of pain\u2010related positive nerve fibres and expression of TRPV1 in subchondral bone. Furthermore, ICA downregulated pain\u2010related Nogo\u2010A\/TRPV1 pathway in the DRG. These findings provide new mechanistic insights into the therapeutic potential of ICA in relieving peripheral nervous system\u2010related chronic pain in KOA.<\/jats:p>","DOI":"10.1111\/jcmm.70223","type":"journal-article","created":{"date-parts":[[2024,12,2]],"date-time":"2024-12-02T22:54:36Z","timestamp":1733180076000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Validation of Peripheral Neuromodulation Mechanisms of Icariin in Knee Osteoarthritis\u2013Related Chronic Pain"],"prefix":"10.1111","volume":"28","author":[{"given":"Dezun","family":"Ma","sequence":"first","affiliation":[{"name":"Academy of Integrative Medicine Fujian University of Traditional Chinese Medicine  Fuzhou Fujian China"},{"name":"Fujian Key Laboratory of Integrative Medicine on Geriatrics  Fuzhou Fujian 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